Proton therapy shows promise for recurrent lung cancer

March 20, 2017

Intensity-modulated proton therapy conferred durable control with minimal toxicity among patients with recurrent thoracic cancer, according to results of a retrospective study presented at the Multidisciplinary Thoracic Cancers Symposium.

These results suggest this technique may offer a safe and effective treatment option for patients with recurrent disease, who traditionally have been deemed ineligible for curative treatment.

Jennifer Ho

“Our study is the first to show that [intensity-modulated proton therapy (IMPT)] can be safe and effective for these patients and that it offers these patients a chance for lasting cancer control without adding significant toxicity,” Jennifer Ho, MD, resident in radiation oncology at The University of Texas MD Anderson Cancer Center, said during a press conference.

Treating patients with local recurrence is a constant challenge and, usually, patients are not offered a second round of radiation.

“There have been concerns about giving reirradiation because the accumulative radiation dose can cause toxicity in normal organs of the chest,” Ho said. “Older techniques studying reirradiation — even lower doses — resulted in anywhere from 20% to 30% rates of serious toxicity. Historically, patients were typically either not offered repeat radiation or only offered palliative reirradiation with lower doses.”

New radiation techniques have emerged that present additional options for these patients.

“IMPT has an advantage over the traditional intensity-modulated radiation therapy because it is able to deposit all of the dose inside of the tumor with no exit dose on the other side, lowering the dose of radiation to other tissue,” Ho said.

Ho and colleagues examined medical records of 27 patients with thoracic tumors who underwent reirradiation with IMPT at MD Anderson Cancer Center between 2011 and 2016. Each patient was treated with definitive — not palliative — intent. Most patients (81%) had non–small cell lung cancer.

The median time to reirradiation was 29.5 months (range, 0.1-212). The median radiation dose was 66 Gy (range, 43.2-84), delivered in 2-Gy fractions.

The median follow-up for all patients was 11.2 months.

Median OS following IMPT reirradiation was 18 months.

At 1-year posttreatment, 78% of patients were free from local failure, and 61% were free from local and regional relapse. One-year PFS was 51% and 1-year OS was 54%; four patients experienced a local recurrence within 1 year of treatment (15%).

“We had excellent freedom from local failure,” Ho said. “We also evaluated the impact of the dose given at reirradiation to see if there was an association, and it appeared significant. Interestingly, patients who received higher or equal to 66 Gy had no local failures.”

Patients who received IMPT doses at or above the population median were twice as likely to be free from local failure as patients who received a lower dose (100% vs. 49%; P = .01). Further, a greater proportion of patients who received higher doses remained free from local and regional failure (84% vs. 23%; P = .035). One-year PFS also was higher among patients who received the higher dose (76% vs. 14%; P = .05).

Two patients (7%) experienced grade 3 or worse long-term lung toxicity. There were no grade 4 or grade 5 toxicities.

“We observed excellent outcomes for toxicity,” Ho said. “Only 7% had serious grade 3 pulmonary toxicity, meaning they required oxygen for their symptoms, and we were impressed that we had no grade 3 or higher toxicity from esophagitis.”

Thus, reirradiation appeared well tolerated and safe, with low toxicity compared with other studies that showed 33% rate of toxicity, Ho said.

“Overall, IMPT is an excellent choice for reirradiation ... and can be particularly useful when giving radiation to more challenging cancers,” she added. – by Melinda Stevens

Disclosures: Ho reports no relevant financial disclosures. One researcher reports grants from Elekta, Genentech, Hitachi, Peregrine Pharmaceuticals and STCube Pharmaceuticals, as well as honoraria from AstraZeneca, ProCure and US Oncology.

Intensity-modulated proton therapy conferred durable control with minimal toxicity among patients with recurrent thoracic cancer, according to results of a retrospective study presented at the Multidisciplinary Thoracic Cancers Symposium.

These results suggest this technique may offer a safe and effective treatment option for patients with recurrent disease, who traditionally have been deemed ineligible for curative treatment.

Jennifer Ho

“Our study is the first to show that [intensity-modulated proton therapy (IMPT)] can be safe and effective for these patients and that it offers these patients a chance for lasting cancer control without adding significant toxicity,” Jennifer Ho, MD, resident in radiation oncology at The University of Texas MD Anderson Cancer Center, said during a press conference.

Treating patients with local recurrence is a constant challenge and, usually, patients are not offered a second round of radiation.

“There have been concerns about giving reirradiation because the accumulative radiation dose can cause toxicity in normal organs of the chest,” Ho said. “Older techniques studying reirradiation — even lower doses — resulted in anywhere from 20% to 30% rates of serious toxicity. Historically, patients were typically either not offered repeat radiation or only offered palliative reirradiation with lower doses.”

New radiation techniques have emerged that present additional options for these patients.

“IMPT has an advantage over the traditional intensity-modulated radiation therapy because it is able to deposit all of the dose inside of the tumor with no exit dose on the other side, lowering the dose of radiation to other tissue,” Ho said.

Ho and colleagues examined medical records of 27 patients with thoracic tumors who underwent reirradiation with IMPT at MD Anderson Cancer Center between 2011 and 2016. Each patient was treated with definitive — not palliative — intent. Most patients (81%) had non–small cell lung cancer.

The median time to reirradiation was 29.5 months (range, 0.1-212). The median radiation dose was 66 Gy (range, 43.2-84), delivered in 2-Gy fractions.

The median follow-up for all patients was 11.2 months.

Median OS following IMPT reirradiation was 18 months.

At 1-year posttreatment, 78% of patients were free from local failure, and 61% were free from local and regional relapse. One-year PFS was 51% and 1-year OS was 54%; four patients experienced a local recurrence within 1 year of treatment (15%).

“We had excellent freedom from local failure,” Ho said. “We also evaluated the impact of the dose given at reirradiation to see if there was an association, and it appeared significant. Interestingly, patients who received higher or equal to 66 Gy had no local failures.”

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Patients who received IMPT doses at or above the population median were twice as likely to be free from local failure as patients who received a lower dose (100% vs. 49%; P = .01). Further, a greater proportion of patients who received higher doses remained free from local and regional failure (84% vs. 23%; P = .035). One-year PFS also was higher among patients who received the higher dose (76% vs. 14%; P = .05).

Two patients (7%) experienced grade 3 or worse long-term lung toxicity. There were no grade 4 or grade 5 toxicities.

“We observed excellent outcomes for toxicity,” Ho said. “Only 7% had serious grade 3 pulmonary toxicity, meaning they required oxygen for their symptoms, and we were impressed that we had no grade 3 or higher toxicity from esophagitis.”

Thus, reirradiation appeared well tolerated and safe, with low toxicity compared with other studies that showed 33% rate of toxicity, Ho said.

“Overall, IMPT is an excellent choice for reirradiation ... and can be particularly useful when giving radiation to more challenging cancers,” she added. – by Melinda Stevens

Disclosures: Ho reports no relevant financial disclosures. One researcher reports grants from Elekta, Genentech, Hitachi, Peregrine Pharmaceuticals and STCube Pharmaceuticals, as well as honoraria from AstraZeneca, ProCure and US Oncology.

Perspective

Pranshu Mohindra

Ho and colleagues evaluated patients with locally recurrent lung cancer. Historically, treatment outcomes for these patients have been limited due to high risk for toxicity. Surgery is considered challenging in this population. Similarly, reirradiation — repeat courses of radiation targeting the same region — for thoracic tumors is difficult using conventional radiation techniques because the normal tissues (mainly spinal cord, lungs, heart and esophagus) may have “memory” of damage from the prior course of radiation. Chemotherapy response rates for this population are also very poor, and such patients are often directed to palliative treatment approaches.

Ho and colleagues provide the first clinical report of outcomes using a highly modern form of radiation therapy — intensity modulated proton therapy (IMPT) — for reirradiation of thoracic cancers. In the study, the estimated local control at 1 year was 78%, which is among the highest reported in this setting.

Protons have unique physical characteristics, which make them an exciting option for treatment of tumors at critical locations, as in thoracic cancers. IMPT is an even more advanced form of the proton beam therapy.

Eighty-five percent of patients in this study received a radiation dose of 60 Gy or more. The standard dose for primary treatment of locally advanced non–small cell lung cancer is 60 Gy. To be able to administer more than 60 Gy in a reirradiation setting at such high safety is impressive.

One of the biggest limitations of proton beam therapy in thoracic tumors is related to breathing motion and the rapid change of tissue density at the air-tissue interface. In the reirradiation setting, however, tumor regions typically demonstrate only limited motion due to fibrosis from the prior course of radiation. This reduces any uncertainty with proton beam therapy, especially with IMPT technique, making treatment plans more robust and giving clinicians an opportunity to limit doses to surrounding tissues with high precision.

It would be important to note that proton beam therapy can not complete exclude the risk for serious toxicity that might come from irradiation of tissues within the target volume. For example, if the recurrent tumor surrounds major airways or blood vessels, then any form of reirradiation, including proton beam therapy, will require treatment of the target region including these normal tissues. Hence, there is still a risk for serious toxicity that needs to be discussed with the patient. Unfortunately, there are only limited options to prevent or treat such complications, and more research is needed to develop radioprotectors. Until then, carefully selected patients will benefit from use of reirradiation with IMPT. Continued reporting of such long-term outcomes with IMPT will guide future practices and research. At this point, there are only a handful of centers across the country with this ability. However, more centers are in development, and it would help if practitioners would consider referral of appropriate patients to centers with this ability so the patients can have a detailed discussion of risks/benefits with their providers.